Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

Diindolylmethane in Healthy Volunteers

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase I Biomarker/Laboratory analysis, Prevention Active 18 to 70 NCI KUMC-HSC-9139-3 HSC # 9139, NCT00392652

Objectives

Primary

1. Determine the effect of multiple daily dosing with nutritional-grade, absorption-enhanced diindolylmethane (BR-DIM™) on the disposition of probe drugs metabolized by cytochrome P4501A2 (CYP1A2) and CYP3A4 in healthy volunteers.

Secondary

1. Determine the effect of BR-DIM™ on estrogen metabolites in urine and on activities of CYP2C9, CYP2D6, and P-glycoprotein/OATP.
2. Determine the effect of a single dose of BR-DIM™ on the disposition of probe drugs that are metabolized or transported by CYP1A2, CYP2C9, CYP2D6, CYP3A4, and P-glycoprotein.
3. Determine the safety and tolerability of single and multiple daily doses of this drug in healthy volunteers.
4. Determine the pharmacokinetics of a single dose of BR-DIM™ and of the same dose after chronic daily dosing.
5. Determine the effects of BR-DIM™ on activities of glutathione-S-transferase, a phase 2 enzyme, in lymphocytes.

Entry Criteria

Disease Characteristics:

• Healthy men and women



• Nonsmoker confirmed by urine cotinine test



• No active malignancy

Prior/Concurrent Therapy:

• No investigational drugs within the past 3 months
• No prior chemotherapy
• No concurrent regular medications or hormones
  • No recent change in medications or dosage of medications
• No concurrent regular supplements or vitamins
• No concurrent over-the-counter medications
• No concurrent grapefruit or its juice

Patient Characteristics:

• Life expectancy ≥ 12 months
• Hemoglobin > 10 g/dL
• Absolute granulocyte count > 1,500/mm³
• Creatinine < 2.0 mg/dL
• Albumin > 3.0 g/dL
• Bilirubin < 1.8 mg/dL
• AST and ALT < 110 U/L
• Alkaline phosphatase < 300 U/L
• Body mass index ≤ 30
• Not pregnant or nursing
• Negative pregnancy test
• Fertile participants must use effective nonhormonal contraception
• No acute, unstable, chronic, or recurring medical conditions
• No strict vegetarians or consumption of > 3 medium servings (½ cup each) of cruciferous vegetables per week
  • Participants who have stopped eating cruciferous vegetables within the past 2 weeks and agree to refrain from eating them for the duration of the study are eligible
  • Cruciferous vegetables include broccoli, cabbage (including coleslaw), cauliflower, bok-choy, brussels sprouts, collards, kale, kohlrabi, mustard greens, rutabaga, turnip, and watercress
• No serious drug allergies or other serious intolerance or allergies
  • Mild seasonal allergies allowed
• No chronic conditions, including headaches, dysphoria, fatigue, dizziness, blurred vision, insomnia, rhinorrhea, nausea, vomiting, abdominal pain, diarrhea, constipation, menopausal hot flashes/night sweats, or clinically significant premenstrual syndrome
• No serious acute or chronic illness
• No requirement for chronic drug therapy
• No alcohol ingestion within 48 hours of study treatment

Expected Enrollment

A total of 14 participants will be accrued for this study.

Outcomes

Effect of diindolymethane (BR-DIM™) on activities of CYP3A4 and CYP1A2
Toxicity

Estrogen metabolites in urine and activities of CYP2C9, CYP2D6, P-glycoprotein/OATP, and glutathione-S-transferase
Safety and tolerability
Pharmacokinetics

Outline

This is a randomized, double-blind study. Participants are stratified according to gender. Participants are randomized to 1 of 2 intervention arms.

• Arm I: Participants receive low-dose oral diindolylmethane (BR-DIM™) twice daily for 4 weeks.



• Arm II: Participants receive high-dose oral BR-DIM™ twice daily for 4 weeks.

In both arms, participants receive an oral probe-drug cocktail comprising caffeine (CYP1A2), dextromethorphan (CYP2D6), buspirone (CYP3A4), losartan (CYP2C9), and fexofenadine (P-glycoprotein) before randomization and after the first and last dose of BR-DIM™.

Blood and urine are collected periodically for pharmacokinetic profiles of BR-DIM™ and probe drugs.

After completion of study intervention, participants are followed at 1 week.

Trial Contact Information

Trial Lead Organizations

Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center

Gregory Reed, PhD, Principal investigator		Ph: 913-588-6020

U.S.A.
Kansas
	Kansas City
	Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center
		Gregory Reed, PhD	Ph:  913-588-7513

Registry Information
Official Title		Phase 1 Multiple-Dose Safety, Pharmacokinetic, and Drug Interaction Clinical Study of Nutritional-Grade, Absorption-Enhanced DIM (BR-DIM)
Trial Start Date		2006-11-20
Registered in ClinicalTrials.gov		NCT00392652
Date Submitted to PDQ		2006-09-06
Information Last Verified		2008-04-20
NCI Grant/Contract Number		CN35008